What investigations are recommended for a first episode of psychosis according to Australian guidelines?

First Episode Psychosis Investigations - Australian Guidelines

For first episode psychosis in Australia, perform a comprehensive medical workup including: full blood count, electrolytes, renal and liver function, thyroid function, glucose, lipids, prolactin, urine drug screen, and consider neuroimaging (CT or MRI brain) only when there are neurological signs, atypical presentation, or abnormal examination findings—not routinely.

Core Investigation Framework

Universal Investigations (Perform in All Cases)

The following investigations should be conducted for every patient presenting with first episode psychosis 1:

• Blood tests:

  • Full blood count (FBC)
  • Electrolytes, urea, creatinine
  • Liver function tests (LFTs)
  • Thyroid function tests (TSH, free T4)
  • Fasting glucose and HbA1c
  • Fasting lipid profile
  • Prolactin level
  • Calcium and phosphate

• Urine drug screen - to exclude substance-induced psychosis, particularly cannabis, amphetamines, and other psychoactive substances 1

• Pregnancy test - for females of childbearing age

• Baseline metabolic monitoring - weight, height, BMI, waist circumference, blood pressure 1

Targeted Investigations (Based on Clinical Indicators)

Neuroimaging (CT or MRI brain) should be performed selectively, not routinely 2, 3:

• Indications for neuroimaging:
  • Focal neurological signs or deficits
  • Cognitive impairment beyond what is expected
  • Atypical presentation (e.g., age >40 years, sudden onset, altered consciousness)
  • Abnormal neurological examination
  • History of head trauma
  • New-onset seizures
  • Headache with concerning features

Critical caveat: Australian guidelines have historically recommended routine neuroimaging, but recent evidence challenges this practice. Studies show that while 20-26% of scans reveal abnormalities, only 0-3.3% are causally related to psychosis, and only 1.2-3.5% lead to changes in management 2, 3, 4. The yield is particularly low in young patients (18-40 years) without neurological signs 2, 3.

Low-Yield Investigations (Consider Based on Clinical Suspicion)

• Electroencephalogram (EEG) - only if seizure activity suspected; routine EEG shows abnormalities in only 9% of cases, rarely with clinical significance 3

• Autoimmune screening (including anti-NMDA receptor antibodies, anti-glutamic acid decarboxylase antibodies):

  • Only if clinical features suggest autoimmune encephalitis (rapid onset, seizures, movement disorders, autonomic instability, decreased consciousness)
  • Anti-GAD antibody screening is NOT recommended routinely - prevalence in psychosis populations (0.7%) is not significantly different from controls (1.0%), and all positive cases are low-titre without meeting encephalitis criteria 5

• Syphilis serology (RPR/TPPA) - if risk factors present or endemic area

• HIV testing - if risk factors present or patient consents

• Vitamin B12 and folate - if dietary deficiency suspected or neurological signs present

• Ceruloplasmin and copper studies - only if Wilson disease suspected (age <40, movement disorder, liver dysfunction, Kayser-Fleischer rings)

Unnecessary Investigations

Do not perform routinely:

• Lumbar puncture (unless CNS infection strongly suspected clinically)
• Extensive autoimmune panels without clinical indicators
• Genetic testing (unless specific syndrome suspected)
• Routine EEG without seizure concerns

Clinical Reasoning Algorithm

Step 1: History and Examination

• Detailed psychiatric history including onset, duration, substance use
• Comprehensive medical history including medications, medical conditions
• Thorough neurological examination
• Mental state examination
• Family history of psychiatric and neurological disorders

Step 2: Universal Investigations

• Perform all baseline blood tests and urine drug screen in every patient
• These exclude common medical causes: thyroid dysfunction, metabolic disturbances, substance intoxication

Step 3: Risk Stratification for Neuroimaging

HIGH RISK (neuroimaging indicated):

• Focal neurological signs
• Cognitive impairment disproportionate to psychosis
• Age >40 years at first presentation
• Altered level of consciousness
• Seizures
• Severe or progressive headache
• Head trauma history

LOW RISK (neuroimaging NOT routinely indicated):

• Age 18-40 years
• Normal neurological examination
• Typical psychotic presentation
• No cognitive impairment beyond expected
• Clear consciousness

Step 4: Targeted Additional Testing

• Only pursue autoimmune or infectious workup if clinical features suggest specific etiologies
• Do not perform "shotgun" testing

Important Caveats

1. Neuroimaging controversy: While some Australian guidelines recommend routine brain imaging 1, the evidence does not support this practice in young patients without neurological signs 2, 3. Clinical judgment should guide imaging decisions, not blanket protocols.

2. Indigenous Australian considerations: Limited specific guidance exists for Indigenous Australians. Consider higher rates of certain medical comorbidities (diabetes, cardiovascular disease, infectious diseases) when interpreting results 1.

3. Documentation: Poor documentation of physical examination findings (particularly involuntary movements and weight) is common in practice—ensure thorough baseline assessment 3.

4. Timing: Investigations should be completed early in the assessment process to exclude secondary causes before committing to long-term antipsychotic treatment.

5. MRI vs CT preference: When neuroimaging is indicated, MRI is preferred over CT for detecting subtle structural abnormalities, small infarcts, inflammatory lesions, and temporal lobe pathology 6, 7. However, CT is appropriate for acute presentations requiring rapid exclusion of hemorrhage or mass effect.